Individual prediction of lateral neck metastasis risk in patients with unifocal papillary thyroid carcinoma

IntroductionMuch controversy exists over whether to perform lateral neck dissection (LND) on patients with papillary thyroid carcinoma (PTC). This study aimed to build predictive nomograms that could individually estimate lateral neck metastasis (LNM) risk and help determine follow up intensity.Patients and methodsUnifocal PTC patients who underwent LND between April 2012 and August 2014 were identified. Clinical and pathological variables were retrospectively evaluated using univariate and stepwise multivariate logistic regression analysis. Variables that had statistical significance in final multivariate logistic models were chosen to build nomograms, which were further corrected using the bootstrap resampling method.ResultsIn all, 505 PTC patients were eligible for analysis. Among these, 178 patients (35.2%) had lateral neck metastasis. Two nomograms were generated: nomogram (c) and nomogram (c + p). Nomogram (c) incorporated four clinical variables: age, tumor size, tumor site, and extrathyroidal extension (ETE). It had a good discriminative ability, with a C-index of 0.79 (bootstrap-corrected, 0.78). Nomogram (c + p) incorporated two clinical variables and two pathological variables: tumor size, tumor site, extranodal extension (ENE), and number of positive nodes in the central compartment. Nomogram (c + p) showed an excellent discriminative ability, with a C-index of 0.86 (bootstrap-corrected, 0.85).ConclusionTwo predictive nomograms were generated. Nomogram (c) is a clinical model, whereas nomogram (c + p) is a clinicopathological model. Each nomogram incorporates only four variables and can give an accurate estimate of LNM risk in unifocal PTC patients, which may assist clinicians in patient counseling and decision making regarding LND.     

Differentiated Thyroid Cancer in Children: A UK Multicentre Review and Review of the Literature

Aims

To obtain an overview of the management and outcomes of children aged 18 years or younger diagnosed with differentiated thyroid carcinoma of follicular cell origin across the UK, by collecting and analysing data from the limited number of centres treating these patients. This multicentre data might provide a more realistic perspective than single-institution series.

妊娠期甲状腺癌多学科综合治疗

妊娠期甲状腺癌的诊治是目前甲状腺疾病诊治的热点和难点问题之一。妊娠期发现甲状腺癌对临床医生和孕妇都是一个极大的挑战，应通过多学科协作，尽快明确诊断，全面、合理的评估孕妇和胎儿的情况，选择最合适的治疗和随诊方式，避免对孕妇和胎儿产生副反应，维持正常孕期，获得最佳的治疗效果。     

2010年-2018年甲状腺结节相关SCI论文知识图谱及数据可视化分析

目的:分析2010年至2018年甲状腺结节相关SCI论文，并建模进行定性与定量分析。方法:利用文献计量学中的引文分析、共被引分析、数据可视化、聚类分析等方法，使用CiteSpace分析工具，分析来源于Web of ScienceTM核心合集数据库中有关论文的出版情况、国家、机构、作者、知识基础与研究热点。结果:到2018年10月31日截止，研究了4 618篇论文。发表论文数:美国在国家/地区中排名第一，延世大学在研究机构中排名第一，Kwak JY在所有作者中排名第一。从2010年开始，每年发表的论文数量都在稳步增长，有相当多的论文发表在如《新英格兰杂志》、《THYROID》、《JAMA》、《CELL》等高影响因子的期刊上。甲状腺结节的SCI论文参考文献聚类为6类，分别是papillary-like nuclear feature、current statu、radiofrequency ablation、ultrasound elastography、goiter area、data system。代表研究前沿的关键词是meta-analysis、recommendation、thyroid carcinoma、shear wave elastography与bethesda system。结论:本文通过对国际上甲状腺结节的研究基础、研究热点的分析，阐述了甲状腺结节的研究趋势，为我国医学工作者的研究提供参考。     

Protection of White Leghorn chickens by recombinant fowlpox vector vaccine with an updated H5 insert against Mexican H5N2 avian influenza viruses

Despite decades of vaccination, surveillance, and biosecurity measures, H5N2 low pathogenicity avian influenza (LPAI) virus infections continue in Mexico and neighboring countries. One explanation for tenacity of H5N2 LPAI in Mexico is the antigenic divergence of circulating field viruses compared to licensed vaccines due to antigenic drift. Our phylogenetic analysis indicates that the H5N2 LPAI viruses circulating in Mexico and neighboring countries since 1994 have undergone antigenic drift away from vaccine seed strains. Here we evaluated the efficacy of a new recombinant fowlpox virus vector containing an updated H5 insert (rFPV-H5/2016), more relevant to the current strains circulating in Mexico. We tested the vaccine efficacy against a closely related subcluster 4 Mexican H5N2 LPAI (2010 H5/LP) virus and the historic H5N2 HPAI (1995 H5/HP) virus in White Leghorn chickens. The rFPV-H5/2016 vaccine provided hemagglutinin inhibition (HI) titers pre-challenge against viral antigens from both challenge viruses in almost 100% of the immunized birds, with no differences in number of birds seroconverting or HI titers among all tested doses (1.5, 2.0, and 3.1 log₁₀ mean tissue culture infectious doses/bird). The vaccine conferred 100% clinical protection and a significant decrease in oral and cloacal virus shedding from 1995 H5/HP virus challenged birds when compared to the sham controls at all tested doses. Virus shedding titers from vaccinated 2010 H5/LP virus challenged birds significantly decreased compared to sham birds especially at earlier time points. Our results confirm the efficacy of the new rFPV-H5/2016 against antigenic drift of LPAI virus in Mexico and suggest that this vaccine would be a good candidate, likely as a primer in a prime-boost vaccination program.     

Biasing human epidermal growth factor receptor 4 (HER4) tyrosine kinase signaling with antibodies: Induction of cell death by antibody‐dependent HER4 intracellular domain trafficking

Human epidermal growth factor receptor 4 (HER4) isoforms have oncogenic or tumor suppressor functions depending on their susceptibility to proteolytic cleavage and HER4 intracellular domain (4ICD) translocation. Here, we report that the neuregulin 1 (NRG1) tumor suppressor mechanism through the HER4 JMa/CYT1 isoform can be mimicked by the agonist anti‐HER4 Ab C6. Neuregulin 1 induced cleavage of poly(ADP‐ribose) polymerase (PARP) and sub‐G₁ DNA fragmentation, and also reduced the metabolic activity of HER3^?/HER4⁺ cervical (C‐33A) and ovarian (COV318) cancer cells. This effect was confirmed in HER4 JMa/CYT1‐, but not JMa/CYT2‐transfected BT549 triple‐negative breast cancer cells. Neuregulin 1 favored 4ICD cleavage and retention in mitochondria in JMa/CYT1‐transfected BT549 cells, leading to reactive oxygen species (ROS) production through mitochondrial depolarization. Similarly, the anti‐HER4 Ab C6, which binds to a conformational epitope located on a.a. 575‐592 and 605‐620 of HER4 domain IV, induced 4ICD cleavage and retention in mitochondria, and mimicked NRG1‐mediated effects on PARP cleavage, ROS production, and mitochondrial membrane depolarization in cancer cells. In vivo, C6 reduced growth of COV434 and HCC1187 tumor cell xenografts in nude mice. Biasing 4ICD trafficking to mitochondria with anti‐HER4 Abs to mimic NRG1 suppressor functions could be an alternative anticancer strategy.     

Papillary thyroid carcinoma with a high tumor mutation burden has a poor prognosis

BackgroundTumor mutation burden (TMB) as a prognostic marker for immunotherapy has shown prognostic value in many cancers. However, there is no systematic investigation on TMB in papillary thyroid carcinoma (PTC).MethodsBased on the somatic mutation data of 487 PTC patients from The Cancer Genome Atlas (TCGA), TMB was calculated, and we classified the samples into high-TMB (H-TMB) and low-TMB (L-TMB) groups. Bioinformatics methods were used to explore the characteristics and potential mechanism of TMB in PTC.ResultsHigh TMB predicts shorter progression-free survival (PFS) (P < 0.001). TMB was positively correlated with age, stage, tumor size, metastasis, the male sex and tall cell PTC. Compared to the L-TMB group, the H-TMB group presented with lower immune cell infiltration, a higher proportion of tumor-promoting immune cells (M0 macrophages, activated dendritic cells and monocytes) and a lower proportion of antitumor immune cells (M1 macrophages, CD8⁺ T cells and B cells). Additionally, the characteristics displayed by different TMB groups were not driven by critical driver mutations such as BRAF and RAS.ConclusionsPTC patients with high TMB have a worse prognosis. By stratifying PTC patients according to their TMB, advanced PTC patients who are candidates for immunotherapy could be selected.     

抗中性粒细胞胞浆抗体在儿童闭塞性细支气管炎病情评估中的价值

目的 探讨抗中性粒细胞胞浆抗体（ANCA）在儿童闭塞性细支气管炎（BO）病情评估中的临床价值。方法 前瞻性选取2009年6月至2014年10月诊断为BO的患儿59例为研究对象，应用酶联免疫吸附法检测患儿血清中的髓过氧化物酶（MPO）及蛋白酶3（PR3）ANCA的浓度，根据其结果将患儿分为ANCA双阴性组（n=22）、ANCA单阳性组（n=17）及ANCA双阳性组（n=20）。比较入院时各组患儿的BO发生危险因素、临床症状、胸部高分辨CT（HRCT）及肺部病理学评分，以及ANCA表达水平及临床症状、胸部HRCT评分随时间的变化。结果 ANCA双阳性组患儿的BO危险因素评分明显高于ANCA双阴性组（P < 0.05），ANCA单阳性组及双阳性组的临床症状、胸部HRCT及肺部病理学评分均高于ANCA双阴性组（P < 0.05）。患儿出院后随访6个月，MPO-ANCA、PR3-ANCA滴度水平均较入院时和出院时降低（P < 0.05）；其临床症状评分亦低于入院时（P < 0.05），但胸部HRCT评分与入院时比较差异无统计学意义（P > 0.05）；ANCA单阳性组及双阳性组的临床症状评分仍高于ANCA双阴性组（P < 0.05）。结论 ANCA表达水平与BO患儿的病情严重程度具有相关性，对病情评估有一定的临床意义。